Published ahead of print on July 19, 2007, doi:10.1164/rccm.200610-1491OC Am. J. Respir. Crit. Care Med., Volume 176, Number 12, December 2007, 1261-1268 A more recent version of this article appeared on December 15, 2007
Submitted on October 18, 2006 Intratracheal Transplantation of Alveolar Type II Cells Reverse Bleomycin-Induced Lung FibrosisAnna Serrano-Mollar1*,1 Department of Experimental Pathology, Institut d'Investigacions Biomediques de Barcelona, Consejo Superior de Investigaciones Cientificas, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain, 2 Servei de Pneumologia, CIBER, Hospital Clinic, Institut Clinic del Torax, Barcelona, Spain * To whom correspondence should be addressed. E-mail: amsbam{at}iibb.csic.es.
Rationale: Transplant of stem cells has been proposed as a strategy for fibrosis lung repair. Nevertheless, many studies have yielded controversial results that currently limit the potential use of these cells as an efficient treatment. Alveolar type II cells are the progenitor cells of the pulmonary epithelium and usually proliferate following epithelial cell injury. During lung fibrosis, however the altered regeneration process leads to the uncontrolled fibroblast proliferation. Objectives: To investigate whether the intratracheal transplantation of isolated alveolar type II cells can halt and reverse the fibrosis process in an experimental model of bleomycin-induced lung fibrosis in rats. Methods: Lung fibrosis was induced in isogenic female Lewis rats by a single intratraqueal instillation of 2.5 U/kg of bleomycin. Animals were transplanted with the alveolar type II cells from male animals at a dose of 2.5x106 cells/animal, 3, 7 and 15 days after endotracheal bleomycin instillation. Animals were sacrificed 21 days after the induction of lung fibrosis. Measurements and Main Results: Lung fibrosis was assessed by histological study and determination of hydroxyproline content. Engraftment of transplanted cells was measured by Real-time PCR for the Y chromosome and by the fluorescent in situ hybridazation for the Y chromosome. Transplantation of alveolar type II cells into the damaged lung at 3, 7 or 15 days after bleomycin instillation lead to a reduced collagen deposition, and reduction in the severity of pulmonary fibrosis. Conclusion: This study demonstrates the potential role of the alveolar type II cells transplantation in designing future therapies of lung fibrosis. Key words: Cell therapy, lung epithelium, lung repair.
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
